Experimental diabetes in animals can be cured by transplantation of isolated islets of Langerhans or dissociated neonatal pancreas. Renal lesions secondary to diabetes in experimental animals can also be stabilized or reversed by successful islet transplantation. Islet tissue can be obtained from adult human cadaver pancreata that is viable (as judged by ability to release insulin following glucose stimulation in vitro) and is relatively pure (as judged by the ratio of insulin to amylase in the isolated tissue). Infant human cadaver pancreas has been found to have a very low exocrine digestive enzyme content and a relatively high islet tissue content. Infant pancreas is easily dissociated into fragments that are not autolytic or proteolytic, and is an ideal source of islet tissue for transplantation. We propose to perform islet transplantation in individuals with juvenile onset diabetes who have already received a renal allograft because of end stage diabetic nephropathy. These individuals are already receiving immunosuppressive therapy; following an islet transplant they will assume no added risks as far as immunosuppression is concerned. The objective will be restoration of normal carbohydrate metabolism. These individuals will be evaluated pre-transplant for insulin requirement, plasma C-peptide levels following a glucose challenge, and the status of disease processes associated with diabetes in the eyes, nervous, vascular, and renal systems. Transplantation will be into the portal vein (the most effective site in animals) with a quantity of tissue not raising portal pressure or affecting hepatic function; any excess tissue not accommodated by the portal vein will be transplanted intraperitoneally. Post transplant, abolition of insulin requirements will be evidence of successful transplantation. In individuals still requiring insulin, plasma C-peptide levels (C-peptide is not present in commercial U-100 insulin) following glucose stimulation can be compared with pre-transplant levels to provide objective evidence for or against transplanted islet function. All patients will be assessed for progression of diabetic retinopathy, neuropathy, angiopathy, and nephropathy during months and years of followup to determine the effect of islet transplantation on disease processes associated with diabetes.